180695-80-1Relevant articles and documents
Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor
England, Katherine S.,Tumber, Anthony,Krojer, Tobias,Scozzafava, Giuseppe,Ng, Stanley S.,Daniel, Michelle,Szykowska, Aleksandra,Che, Kahing,Von Delft, Frank,Burgess-Brown, Nicola A.,Kawamura, Akane,Schofield, Christopher J.,Brennan, Paul E.
, p. 1879 - 1886 (2014)
A potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound 35, pIC50 7.2) with excellent selectivity over representatives from other KDM subfamilies has been developed; the discovery that a triazolopyridine compound binds to the active site of JmjC KDMs was followed by optimisation of the triazole substituent for KDM2A inhibition and selectivity. This journal is
Novel histone deacetylase inhibitors bearing a 4-piperidin-4-yl-triazole scaffold as antitumor agents
Wang, Yan,Su, Li,Wang, Qiang,Zhang, Li,Luan, Yepeng
, p. 52 - 61 (2020)
Histone deacetylases have proven to be promising targets for the development of anticancer drugs. In this work, we reported the design and synthesis of a series of 20 novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core structure. Five newly obtained compounds displayed excellent HDAC6 inhibitory activities. Among them, compounds WY-12 and WY-15 also exhibited excellent antiproliferative activities against six human tumor cell lines. WY-15 could increase the level of acetylated histone H3 in a dose-dependent manner. Furthermore, WY-15 remarkably induced cell cycle arrest of Sy5y cancer cells in G0/G1 phase. Finally, the high potency of compound WY-15 toward HDAC6 was rationalized by molecular docking study.
Covalent Allosteric Inhibitors of Akt Generated Using a Click Fragment Approach
Green, Ivan R.,Landel, Ina,Lindemann, Marius,Müller, Matthias P.,Pelly, Stephen C.,Quambusch, Lena,Rauh, Daniel,Taher, Abu,Uhlenbrock, Niklas,Weisner, J?rn,van Otterlo, Willem A. L.,van der Westhuizen, Leandi
, (2022/03/14)
Akt is a protein kinase that has been implicated in the progression of cancerous tumours. A number of covalent allosteric Akt inhibitors are known, and based on these scaffolds, a small library of novel potential covalent allosteric imidazopyridine-based inhibitors was designed. The envisaged compounds were synthesised, with click chemistry enabling a modular approach to a number of the target compounds. The binding modes, potencies and antiproliferative activities of these synthesised compounds were explored, thereby furthering the structure activity relationship knowledge of this class of Akt inhibitors. Three novel covalent inhibitors were identified, exhibiting moderate activity against Akt1 and various cancer cell lines, potentially paving the way for future covalent allosteric inhibitors with improved properties.
1, 2, 4-OXADIAZOLE DERIVATIVES AND USES THEREOF
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Paragraph 0095, (2020/04/25)
The disclosure provides 1, 2, 4-oxadiazole derivatives useful for stemming bleeding and for treating cancer.
